A Phase Ib Study of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection Plus FOLFIRI in Chinese Patients With Metastatic Colorectal Cancer

NCT02453464 | Unknown Phase 1

• 1 other identifier: SIM129-mCRC-01
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection in combination with FOLFIRI in patients with previously treated metastatic colorectal cancer. This study includes two stages. Stage 1 is the dose-escalation stage. Once the maximum tolerated dose (MTD) of Sevacizumab has been established, additional patients will be enrolled in the cohort-expansion stage (Stage 2).

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  up to 56 days

Secondary Outcomes (9)

• Adverse Events (NCI-CTC 4.0)

  28 days after the last dose

• Plasma pharmacokinetics (PK) parameters for Sevacizumab

  Cycle 1(Day3, Day4, Day7, Day10, Day13); Cycle 2-4(Day1);Cycle 4(Day1, Day2, Day5, Day8 ,Day11)

• Plasma pharmacokinetics (PK) parameters (Cmax, Tmax, AUC, T1/2) for Irinotecan and its major metabolite SN-38

  Day1, Day2, Day3, Day15, Day16, Day17

• Plasma pharmacokinetics (PK) parameters for 5-FU

  Day1, Day3, Day15, Day17

• Potential biomarkers, including VEGF and ADA

  VEGF:Cycle 1(Day3, Day4, Day7, Day10, Day13); Cycle 2-4(Day1);Cycle 4(Day1, Day2, Day5, Day8, Day11); ADA : within 15 minutes before each Sevacizumab administration

Study Arms (1)

Sevacizumab+FOLFIRI

EXPERIMENTAL

Two weeks as one cycle. Cycle 1: FOLFIRI on day1-2, Sevacizumab on day3; Cycle 2 and after: Sevacizumab on day 1, and then FOLFIRI on day1-2

Drug: Sevacizumab; Drug: Irinotecan; Drug: 5-FU; Drug: Leucovorin

Interventions

Sevacizumab DRUG

escalating doses of Sevacizumab : 3mg/kg，4mg/kg，5mg/kg

Sevacizumab+FOLFIRI

Irinotecan DRUG

Irinotecan: IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity

Sevacizumab+FOLFIRI

5-FU DRUG

5-FU: IV solution, IV bolus over 2-4 minutes, 400 mg/m²; IV infusion over 46 hours, 2400 mg/m²; Every 14 days, Until disease progression/toxicity

Sevacizumab+FOLFIRI

Leucovorin DRUG

Leucovorin: IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity

Sevacizumab+FOLFIRI

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological/cytological confirmed unresectable metastatic colorectal cancer patients who have failed first-line oxaliplatin-based chemotherapy
• At least one measurable lesion (according to RECIST 1.1 )
• At least 4 weeks from the last chemotherapy. If patients received anti-tumor biological products, at least four t1/2 of washout period is needed
• Toxicity from previous treatment has to restore to ≤ grade 1 (NCI CTC4.0)
• ECOG performance status 0-1
• Life expectancy ≥ 3 months
• Adequate hematologic function: ANC ≥ 1.5 × 10\^9 /L, HB ≥ 90 g /L (blood transfusion allowed), PLT ≥ 100 ×10\^9 /L; Adequate hepatic function: ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN, TBIL ≤ 1.5 × ULN (patients with liver metastases ALT ≤ 5 × ULN, AST ≤ 5 × ULN); Adequate renal function: creatinine ≤ 1 × ULN; Coagulation function: INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN
• Patients of childbearing potential (male and female) must agree to use reliable methods of contraception until at least 12 weeks after the last dose
• Patients signed written inform consent
• Willingness and capability to communicate with investigators and to comply with protocol requirements

You may not qualify if:

• HCV, TP or HIV antibody positive
• Previously received anti-VEGF protein drugs, such as Bevacizumab,Sevacizumab
• Previously treated with irinotecan
• History of dihydropyrimidine dehydrogenase deficiency
• Patients with alcohol or drug dependence
• Participation in other clinical trials within 4 weeks before enrollment
• Active or chronic hepatitis B infection with HBV DNA \> 1.0 \* 10\^3 IU/mL
• Serious infection requiring intravenous antibiotic therapy
• Symptomatic brain metastases
• Patients with proteinuria at screening (urine protein ≥ 1+)
• History of abdominal fistula, gastrointestinal perforation, abdominal abscess within 6 months prior to enrollment
• History of intestinal obstruction, inflammatory bowel disease, or other intestinal diseases with chronic diarrhea as the major symptom
• Serious non-healing wounds, ulcers or fractures
• Major surgery (excluding biopsy) or significant trauma within 4 weeks prior to enrollment
• Active bleeding within 3 months prior to enrollment

Sponsors & Collaborators

• Jiangsu Simcere Pharmaceutical Co., Ltd.: lead

Study Sites (3)

The First Bethune Hospital of Jilin University

Changchun, Jilin, 130021, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

The First Hospital of Zhejiang Province

Hangzhou, Zhejiang, 310003, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Irinotecan; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Jin Li, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haijun Li, MS

CONTACT

86-025-85560000; lihaijun@simcere.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2015
• First Posted: May 25, 2015
• Study Start: August 1, 2015
• Primary Completion: December 1, 2016
• Last Updated: April 20, 2016

Record last verified: 2016-04

Locations

CN (3)